OBJECTIVE To investigate the mechanism by which Naozhenning granules （NZN） improve learning and memory impairment in a rat model of multiple cerebral concussion （MCC）. METHODS The MCC rat model was established using the closed controlled cortical impact method. The experiment was set up with a blank group （normal saline）， a model group （normal saline）， a piracetam group （positive control group， 0.324 g/kg）， and high-， medium-， and low-dose NZN groups （5.4， 2.7， 1.35 g/kg）， with 11 rats in each group. Drugs or normal saline were administered by gavage once daily for 28 consecutive days. General condition and body weight were monitored throughout the experiment. The sucrose preference rate and novel object recognition index were measured； Evans blue （EB） extravasation in the cerebral cortex was detected； pathological changes of cortical neurons were observed； the levels of B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， interleukin-6 （IL-6）， IL-10， and tumor necrosis factor-α （TNF-α） in the cerebral cortex were determined； and the phosphorylation levels of AMP-activated protein kinase （AMPK）， glycogen synthase kinase 3β （GSK3β）， and Tau protein were detected. RESULTS Compared with the blank group， the model group showed poor mental state， sluggish response to external stimuli， reduced food and water intake， decreased limb flexibility， and disheveled fur. Body weight， sucrose preference rate， and novel object recognition index were significantly decreased （ P ＜0.05）； EB extravasation in the cerebral cortex was significantly increased （ P ＜0.05）， with severe neuronal damage. The positive area ratio of Bax protein， IL-6 and TNF-α levels， and Tau protein phosphorylation level were all significantly increased （ P ＜0.05）， whereas the positive area ratio of Bcl-2 protein， IL-10 level， and AMPK and GSK3β protein phosphorylation levels were significantly decreased （ P ＜0.05）. Compared with the model group， all NZN dose groups showed improvements in general condition and pathological damage， with quantitative indices partially restored， and the differences in quantitative indices in high-dose NZN group were statistically significant （ P ＜0.05）. CONCLUSIONS NZN can effectively improve learning and memory impairment in MCC model rats. The mechanism may be related to activating the AMPK/GSK3β pathway， inhibiting inflammatory response， reducing Tau protein phosphorylation level， and then repairing the neuronal injury.

BACKGROUND:According to different locations of lumbar disc herniation,it can be classified into many types.Among them,patients with intradural sac type lumbar disc herniation have severe clinical symptoms,which greatly affect their quality of life.Therefore,this article studies the risk factors for its onset,and improving the preoperative diagnostic rate is of great significance for the treatment and prevention of this disease.OBJECTIVE:To explore the risk factors for intradural lumbar disc herniation.METHODS:A retrospective analysis was conducted on 15 patients with intradural lumbar disc herniation(herniation group)admitted to three hospitals in Xuzhou city from May 2014 to November 2022.Propensity score matching was used to match patients with lumbar disc herniation who did not protrude into the dura mater in a ratio of 1:4.A total of 59 patients were selected and included in the non-herniation group.Clinical data were observed in the two groups.Univariate and binary logistic regression analysis,multiple linear regression,and PROBIT regression analysis were utilized to identify the relevant risk factors for intradural lumbar disc herniation.RESULTS AND CONCLUSION:(1)The results of univariate analysis showed that the average disease course,proportion of segments,modified Pfiirmann grading,sacral tilt angle,proportion of previous lumbar spine surgery history,and proportion of heavy manual workers,proportion of lumbar spinal stenosis,redundancy of the cauda equina,and ossification of the posterior longitudinal ligament all showed statistical differences in the herniation and non-herniation groups(P＜0.05).(2)Multivariate regression analysis showed that duration of disease,protruding segment,history of lumbar surgery,modified Pfiirmann grading,cauda equina redundancy,and lumbar spinal stenosis were independent risk factors for intradural lumbar disc herniation.(3)Based on the influencing factors,an receiver operating characteristic curve was constructed,with an area under curve of 0.956(95％CI:0.913-0.998),indicating good discrimination.(4)There was a significant correlation between the duration of the disease,the protruded segment,the history of lumbar spine surgery,the modified Pfirmann classification,cauda equina redundancy,lumbar spinal canal stenosis,and the incidence rate of intradural lumbar disc herniation.

BACKGROUND:According to different locations of lumbar disc herniation,it can be classified into many types.Among them,patients with intradural sac type lumbar disc herniation have severe clinical symptoms,which greatly affect their quality of life.Therefore,this article studies the risk factors for its onset,and improving the preoperative diagnostic rate is of great significance for the treatment and prevention of this disease.OBJECTIVE:To explore the risk factors for intradural lumbar disc herniation.METHODS:A retrospective analysis was conducted on 15 patients with intradural lumbar disc herniation(herniation group)admitted to three hospitals in Xuzhou city from May 2014 to November 2022.Propensity score matching was used to match patients with lumbar disc herniation who did not protrude into the dura mater in a ratio of 1:4.A total of 59 patients were selected and included in the non-herniation group.Clinical data were observed in the two groups.Univariate and binary logistic regression analysis,multiple linear regression,and PROBIT regression analysis were utilized to identify the relevant risk factors for intradural lumbar disc herniation.RESULTS AND CONCLUSION:(1)The results of univariate analysis showed that the average disease course,proportion of segments,modified Pfiirmann grading,sacral tilt angle,proportion of previous lumbar spine surgery history,and proportion of heavy manual workers,proportion of lumbar spinal stenosis,redundancy of the cauda equina,and ossification of the posterior longitudinal ligament all showed statistical differences in the herniation and non-herniation groups(P＜0.05).(2)Multivariate regression analysis showed that duration of disease,protruding segment,history of lumbar surgery,modified Pfiirmann grading,cauda equina redundancy,and lumbar spinal stenosis were independent risk factors for intradural lumbar disc herniation.(3)Based on the influencing factors,an receiver operating characteristic curve was constructed,with an area under curve of 0.956(95％CI:0.913-0.998),indicating good discrimination.(4)There was a significant correlation between the duration of the disease,the protruded segment,the history of lumbar spine surgery,the modified Pfirmann classification,cauda equina redundancy,lumbar spinal canal stenosis,and the incidence rate of intradural lumbar disc herniation.

A two-dimensional preparative liquid chromatographic method was developed for purification of constituents from water extract of Armillaria luteo-virens using reversed phase preparative liquid chromatography(RPLC)coupled with hydrophilic interaction liquid chromatography(HILIC). Seven compounds were isolated from fruit bodies of Armillaria luteo-virens, and their structures were identified on the basis of physicochemical and spectroscopic analyses. These compounds were identified as pyroglutamic acid(1), uridine(2), 2′-deoxyuridine(3), uracil(4), guanosine(5), inosine(6), and adenosine(7). All the compounds were purified and identified from fruit bodies of Armillaria luteo-virens for the first time.

Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are a type of newly discovered antibioticresistant bacteria. The rapid pandemic spread of NDM-1 bacteria worldwide (spreading to India, Pakistan, Europe, America, and Chinese Taiwan) in less than 2 months characterizes these microbes as a potentially major global health problem. The drug resistance of NDM-1 bacteria is largely due to plasmids containing the blaNDM-1 gene shuttling through bacterial populations. The NDM-1 enzyme encoded by the blaNDM-1 gene hydrolyzes β-lactam antibiotics, allowing the bacteria to escape the action of antibiotics. Although the biological functions and structural features of NDM-1 have been proposed according to results from functional and structural investigation of its homologues, the precise molecular characteristics and mechanism of action of NDM-1 have not been clarified. Here, we report the three-dimensional structure of NDM-1 with two catalytic zinc ions in its active site. Biological and mass spectroscopy results revealed that D-captopril can effectively inhibit the enzymatic activity of NDM-1 by binding to its active site with high binding affinity. The unique features concerning the primary sequence and structural conformation of the active site distinguish NDM-1 from other reported metallo-β-lactamases (MBLs) and implicate its role in wide spectrum drug resistance. We also discuss the molecular mechanism of NDM-1 action and its essential role in the pandemic of drug-resistant NDM-1 bacteria. Our results will provide helpful information for future drug discovery targeting drug resistance caused by NDM-1 and related metallo-β-lactamases.
Amino Acid Sequence ; Anti-Bacterial Agents ; metabolism ; Binding Sites ; Captopril ; chemistry ; pharmacology ; Catalytic Domain ; Crystallography, X-Ray ; Drug Resistance, Bacterial ; Enterobacteriaceae ; enzymology ; Molecular Sequence Data ; Sequence Alignment ; Sequence Homology, Amino Acid ; beta-Lactamases ; chemistry ; metabolism